• DOI:10.3109/00498258509049103
• Corpus ID: 210051

Metabolic pathways of the anti-hypertensive agent, N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine+ ++ hydrochloride. I. Studies in the rat.

@article{Assandri1985MetabolicPO,
  title={Metabolic pathways of the anti-hypertensive agent, N-(2,5-dimethyl-1H-pyrrol-1-yl)-6-(4-morpholinyl)-3-pyridazinamine+ ++ hydrochloride. I. Studies in the rat.},
  author={Alessandro Assandri and Antonio Perazzi and E Baldoli and Pietro Ferrari and A. Ripamonti and Elvio Bellasio and G. Tuan and Frank J. Zerilli and Giorgio Tarzia},
  journal={Xenobiotica; the fate of foreign compounds in biological systems},
  year={1985},
  volume={15 12},
  pages={
          1069-87
        }
}

• A. Assandri, A. Perazzi, +6 authors G. Tarzia
• Published 1985
• Chemistry, Biology
• Xenobiotica; the fate of foreign compounds in biological systems

The metabolic fate of a new anti-hypertensive, 1-pyrrolyl pyridazinamine, was studied in male Wistar rats after both p.o. and i.v. administration (1 mg/kg). The compound undergoes rapid metabolism, disappearing from the central compartment with a half-life of about 0.5 h. Plasma concn. of the parent drug and its major metabolite I following i.v. and p.o. administration suggest a route-dependent first-pass metabolism. Ten metabolites were isolated from the urine and identified by u.v., i.r., mass and 1H-n.m.r. spectroscopy. The structure of some was confirmed by 13C-n.m.r. and chemical synthesis. All biotransformations are restricted to the pyrrole ring which undergoes oxidative cleavage followed by a series of chemical rearrangements. A minor pathway leads to the formation of methyl sulphinyl and methyl sulphonyl pyrroles. It is suggested that, as with natural indoles, the pyrrole might be oxidized by a 2,3-dioxygenase. The three major metabolites, I, II and IX, along with two minor ones, VI and VII, were inactive when tested i.v. for antihypertensive activity.